Abstract: Selective flocculation separation is one of the most efficient methods for fine mineral separation. To enhance the flocculation selectivity on the surfaces of hydrophilic and hydrophobic minerals, a hydrophobic group such as cetyldimethyl allyl ammonium chloride (C₁₆DMAAC) was introduced within the molecular chain of polyacrylamide (PAM) to synthesize hydrophobically modified polyacrylamide (HMPAM). The effects of different K⁺ and Ca²⁺ concentrations on the in situ adsorption behavior of dispersants such as sodium hexametaphosphate (SHMP) and HMPAM and their effect on hydrophilic and hydrophobic surfaces were studied using dissipative quartz crystal microbalance (QCM-D). The effects of SHMP and HMPAM on the particle size distribution of silicon powder and hydrophobically modified silicon powder with different salinity were analyzed using a laser particle size analyzer. Results indicated that HMPAM exhibited good flocculation selectivity at varying salinity concentrations. When the background solutions were 10 mmol·L⁻¹, 100 mmol·L⁻¹ KCl, and 1 mmol·L⁻¹ CaCl₂, the QCM-D results indicated that no adsorption layer of SHMP was formed on the hydrophobic surface; moreover, the HMPAM was adsorbed on the hydrophobic surface in sequence. With an increase in salinity, the adsorption of HMPAM increased, and the dissipation of the adsorption layer decreased. Moreover, in the background solution of 10 mmol·L⁻¹ CaCl₂, SHMP did not inhibit the adsorption of HMPAM on hydrophobic surfaces, and an adsorption layer with the change of resonant frequency (Δf) of −18.3 Hz was formed. Conversely, a thin and dense adsorption layer of SHMP was generated on the surface of SiO₂ in 100 mmol·L⁻¹ KCl, which inhibited the adsorption of HMPAM. In 10 mmol·L⁻¹ CaCl₂, a dissipative adsorption layer of SHMP was detected on the surface of SiO₂. Furthermore, a relatively dense adsorption layer was deposited after the injection of 10 mmol·L⁻¹ CaCl₂ solution, which also inhibited the adsorption of HMPAM. The results of floc size measurements revealed that the position and shape of the floc size distribution peak of the silica powder did not change with the effect of SHMP and HMPAM in the background solutions of 100 mmol·L⁻¹ KCl and 10 mmol·L⁻¹ CaCl₂, thus indicating that the SHMP inhibited the flocculation of silica powder by HMPAM. The floc size of the hydrophobically modified silica powder increased with the effect of SHMP and HMPAM. Summarily, the effects of SHMP and HMPAM on the particle size distribution of silicon micro powder and hydrophobic silicon micro powder under different salinity were consistent with the results of QCM-D measurements. This study is an important research basis for selecting and developing flocculants for selective flocculation separation.